The stratified squamous epithelium of the mammalian esophagus actively transports sodium and chloride and thus develops a transmural electrical potential difference (P.D.). We have developed a method to measure this P.D. in the human esophagus at the time of intraluminal pressure measurements. Thus, both P.D. and pressure can be recorded simultaneously at the time esophageal manometric testing. The esophageal P.D. of patients with diseases involving the esophageal mucosa (reflux esophagitis, esophageal carcinoma, and Barrett's esophagus) will be measured and compared to normals. The results will be correlated with the biopsy-histologies of the esophagus and with the clinical course. Such a comparison will determine the usefulness of P.D. measurements in the diagnosis and prognosis of esophageal mucosal diseases. To gain further insight into the meaning in the changes in esophageal P.D. in these disease states, we will create animal models of esophagitis by both acutely and chronically perfusing the esophagus of rabbits and opossums with hydrochloric acid. We will make serial masurements of the in vivo P.D. with the manometric technique and in vitro measurements of sodium and chloride transport using the modified Ussing chamber - short-circuit current technique. The changes in P.D. and in sodium and chloride transport will be correlated with changes in histology. The synergistic effects of bile acids, alcohol or salicylates will be investigated in the same model. These studies should give further insight into the pathophysiology of esophagitis and help define the pathophysiology at the cellular level.